(TERT-BUTYLDIMETHYLSILYLOXY)ACETALDEHYDE

Clear colorless to straw colored liquid

To a solution of (COCl)2 (13.7 mL, 162.2 mmol) in anhydrous CH2Cl2 (400 mL) was added DMSO (25.1 mL, 353.9 mmol) at -78 °C under N2. After being stirred for 30 min, a solution of 2-((tert-butyldimethylsilyl)oxy)ethanol (26.0 g, 147.5 mmol) in anhydrous CH2Cl2 (100 mL) was added dropwise. The mixture was stirred at -78 °C for 30 min and then Et3N (102.74 mL, 737.0 mmol) was added dropwise. After being stirred at -78 °C for 30 min, the reaction was allowed to warm to rt and stirred for 1 h. The reaction mixture was acidified with 2 N aqueous HCl solution to pH=4 and then extracted with CH2Cl2 (3 x 400 mL). The combined organic layers were dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to afford 2-((tert-butyldimethylsilyl)oxy)acetaldehyde (34.0 g, 100percent) as a colorless oil. This material was used for the next step directly without further purification.To a solution of CHTo a solution of CH2C12 (1.8 E) cooled to —30° C. was added oxalyl chloride (79.2 g, 52.8 mE, 624 mmol) drop- wise. The mixture was cooled to —78° C., then DMSO (62.5 g, 88.5 mE, 1.25 mmol) was added dropwise. Afier addition, the mixture was stirred at —78° C. for 30 mm. A solution2-((tert-butyldimethylsilyl)oxy)ethanol (100 g, 567 mmol) dissolved in CH2C12 (200 mE) was added slowly at —78°The reaction mixture was stirred at —78° C. for 1 h. Triethylamine (287 g, 395 mE, 2.84 mmol) was added dropwise—78° C. The mixture was stirred at —78° C. for 30 mm and then it overnight. The reaction mixture was washed with water (1 E), 1 N HC1 (2x1 E), saturated aqueous NaHCO3 solution (1 E) and brine (1 E). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give 2-((tert-butyldimethylsilyl)oxy)acet- aldehyde (98.5 g, 99.8percent) as a brown oil, which was used for the next step directly without thither purification. ‘H NMR (CDC13, 400 MHz): ö 9.70 (s, 1H), 4.22 (s, 2H), 0.93 (s, 9H), 0.11 (s, 6H).To a solution of CH2C12 (1.8 L) cooled to -30 °C was added oxalyl chloride (79.2 g, 52.8 mL, 624 mmol) dropwise. The mixture was cooled to -78 °C, then DMSO (62.5 g, 88.5 mL, 1.25 mmol) was added dropwise. After addition, the mixture was stirred at -78 °C for 30 mm. A solution of 2-((tert-butyldimethylsilyl)oxy)ethanol (100 g, 567 mmol) dissolved in CH2C12 (200 mL) was added slowly at -78 °C. The reaction mixtutre was stirred at -78 °C for 1 h. Triethylamine (287 g, 395 mL, 2.84 mmol) was added dropwise at -78 °C. The mixture was stirred at -78 °C for 30 mm and then rt overnight. The reaction mixture was washed with water (1 L), 1 N HC1 (2 x 1 L), saturated aqueous NaHCO3 solution (1 L) and brine (1 L). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give 2-((tert-butyldimethylsilyl)oxy)acetaldehyde (98.5 g, 99.8percent) as a brown oil, which was used for the next step directly without further purification. 1H NMR (CDC13, 400 IVIHz): 5 9.70 (s, 1H), 4.22 (s, 2H), 0.93 (s, 9H), 0.11 (s, 6H).[00203] Step 3: 2-((tert-butyldimethylsilyl)oxy)acetaldehyde [0990] [00204] To a solution of CHThe 164kg-tert-butyl-dimethyl siloxane-ethanol dissolved in petroleum ether was added 282kg of IBX, reflux 15h at 70 After extraction with ether, the organic phase was filtered and the filtrate was collected and heated to boiling under normal pressure distillation to remove the solvent, followed by distillation under reduced pressure of vacuum degree of 10 ~ 20mmHg, 60 ~ 80 collected fractions, i.e. t-butyl dimethyl siloxane-based product acetaldehyde, yield 82percent, purity of 99.97percent.tert-Butyldimethylhydroxyethoxysilane (3.73 g, 21.15 mmol)DMP (10.76 g, 25.37 mmol) was added to a solution of DCM (35 mL).The reaction was stirred for 1.5 h. Add DCM (100 mL), Saturated NaCO3 (140 mL), 10percent Na2S2O3 (140 mL), Saturated NaCO3 (140 mL), Wash with saturated brine (70 mL) and purify by column chromatography (eluent PE: EA = 16:1).tert-Butyldimethylsiloxane acetaldehyde (2.38 g, 13.65 mmol) was obtained in a yield of 65percent.The 2 - [tert-butyl (dimethyl) silicon-based] phenoxy ethanol (18 A) (76.3 g, 433 . 23 mmol) is dissolved in tetrahydrofuran (400 ml) in, addition of deISS - Martin (202.12 g, 476 . 55 mmol), react at room temperature for 4 hours. Add equal volume of saturated aqueous solution of sodium bicarbonate and saturated sodium thiosulfate aqueous solution were (500 ml), stirring at room temperature 1 hour, filtering, the filter cake of ethyl acetate (100 ml × 2) washing, the filtrate of ethyl acetate (400 ml × 2) extraction, the combined organic phase, the organic phase with saturated salt water (400 ml) washing, drying with anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure and the residue of silica gel column chromatography (ethyl acetate/petroleum ether (v/v)=1/40 - 1/10) separating and purifying, to obtain the title compound 2 - [tert-butyl (dimethyl) silicon-based] oxy acetaldehyde (18 B), colorless liquid (39.7 g, yield 52.63percent)Preparation Example 1-99-2(tert-Butyl-dimethyl-silanyloxy)-acetaldehyde 176 mg (1.0 mmol) of the compound obtained from Preparation Example 1-99-1 was dissolved in 10 mL of dichloromethane. To the solution was added 176 mg (1.5 mmol) of N-methylmorpholine N-oxide and 18 mg (0.05 mmol) of TPAP, and stirred for 30 minutes. The reaction mixture was distilled in vacuo to remove a solvent and purified by column chromatography using a mixed solution of hexane and ethyl acetate in the ratio of 9:1 to obtain the title compound 35 mg (20percent).A solution of bis-silyl ether 5 (1.00 g, 3.16 mmol, 1.00 equiv) in CH2Cl2 (21.1 mL) was cooled to –78 °C and ozone was bubbled through until the solution turned blue. N2 gas was then bubbled through the solution until the reaction mixture turned colorless. PPh3 (0.99 g, 3.79 mmol, 1.20 equiv) was then added and the mixture was warmed to 23 °C slowly. The reaction mixture was stirred under N2 for 1.5 h and the solvent was evaporated in vacuo. The residue was purified by silica gel chromatography (1:8 EtOAc:hexanes) to afford aldehyde 6 (1.07 g, 97percent yield).A solution of compound 61.1 (30 g, 100 mmoi) in DCM (300 mL) was treated with ozone at -78°C until the solution turned lightly blue. PPh

Molecular Weight:174.31
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:174.107606347
Monoisotopic Mass:174.107606347
Topological Polar Surface Area:26.3
Heavy Atom Count:11
Complexity:136
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes